TY - JOUR
T1 - Endotoxin disrupts the estradiol-induced luteinizing hormone surge
T2 - Interference with estradiol signal reading, not surge release
AU - Battaglia, Deborah F.
AU - Beaver, Andrew B.
AU - Harris, Thomas G.
AU - Tanhehco, Edmund
AU - Viguié, Catherine
AU - Karsch, Fred J.
PY - 1999
Y1 - 1999
N2 - Three experiments were conducted to investigate whether the immune/inflammatory stimulus endotoxin disrupts the estradiol-induced LH surge of the ewe. Ovariectomized sheep were set up in an artificial follicular phase model in which luteolysis is simulated by progesterone withdrawal and the follicular phase estradiol rise is reproduced experimentally. In the first experiment, we tested the hypothesis that endotoxin interferes with the estradiol-induced LH surge. Ewes were either infused with endotoxin (300 ng/kg/h, iv) for 30 h beginning at onset of a 48-h estradiol stimulus or sham infused as a control. Endotoxin significantly delayed the time to the LH surge (P < 0.01), but did not alter surge amplitude, duration, or incidence. The second experiment tested the hypothesis that the delaying effects of endotoxin on the LH surge depend on when endotoxin is introduced relative to the onset of the estradiol signal. Previous work in the ewe has shown that a 14-h estradiol signal is adequate to generate GnRH and LH surges, which begin 6-8 h later. Thus, we again infused endotoxin for 30 h, but began it 14 h after the onset of the estradiol signal. In contrast to the first experiment, endotoxin given later had no effect on any parameter of the LH surge. In the third experiment, we tested the hypothesis that endotoxin acts during the first 14 h to disrupt the initial activating effects of estradiol. Estradiol was delivered for just 14 h, and endotoxin was infused only during this time. Under these conditions, endotoxin blocked the LH surge in five of eight ewes. In a similar follow-up study, endotoxin again blocked the LH surge in six of seven ewes. We conclude that endotoxin can disrupt the estradiol-induced LH surge by interfering with the early activating effects of the estradiol signal during the first 14 h (reading of the signal). In contrast, endotoxin does not disrupt later stages of signal processing (i.e. events during the interval between estradiol signal delivery and surge onset), nor does it prevent actual hormonal surge output. Thus, endotoxin appears to disrupt estrogen action per se rather than the release of GnRH or LH at the time of the surge.
AB - Three experiments were conducted to investigate whether the immune/inflammatory stimulus endotoxin disrupts the estradiol-induced LH surge of the ewe. Ovariectomized sheep were set up in an artificial follicular phase model in which luteolysis is simulated by progesterone withdrawal and the follicular phase estradiol rise is reproduced experimentally. In the first experiment, we tested the hypothesis that endotoxin interferes with the estradiol-induced LH surge. Ewes were either infused with endotoxin (300 ng/kg/h, iv) for 30 h beginning at onset of a 48-h estradiol stimulus or sham infused as a control. Endotoxin significantly delayed the time to the LH surge (P < 0.01), but did not alter surge amplitude, duration, or incidence. The second experiment tested the hypothesis that the delaying effects of endotoxin on the LH surge depend on when endotoxin is introduced relative to the onset of the estradiol signal. Previous work in the ewe has shown that a 14-h estradiol signal is adequate to generate GnRH and LH surges, which begin 6-8 h later. Thus, we again infused endotoxin for 30 h, but began it 14 h after the onset of the estradiol signal. In contrast to the first experiment, endotoxin given later had no effect on any parameter of the LH surge. In the third experiment, we tested the hypothesis that endotoxin acts during the first 14 h to disrupt the initial activating effects of estradiol. Estradiol was delivered for just 14 h, and endotoxin was infused only during this time. Under these conditions, endotoxin blocked the LH surge in five of eight ewes. In a similar follow-up study, endotoxin again blocked the LH surge in six of seven ewes. We conclude that endotoxin can disrupt the estradiol-induced LH surge by interfering with the early activating effects of the estradiol signal during the first 14 h (reading of the signal). In contrast, endotoxin does not disrupt later stages of signal processing (i.e. events during the interval between estradiol signal delivery and surge onset), nor does it prevent actual hormonal surge output. Thus, endotoxin appears to disrupt estrogen action per se rather than the release of GnRH or LH at the time of the surge.
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U2 - 10.1210/endo.140.6.6739
DO - 10.1210/endo.140.6.6739
M3 - Article
C2 - 10342831
AN - SCOPUS:0033279406
SN - 0013-7227
VL - 140
SP - 2471
EP - 2479
JO - Endocrinology
JF - Endocrinology
IS - 6
ER -